Dimethylpyrazines with methyllithium

The reactions of the isomeric dimethylpyrazines and trimethyl-pyrazine with methyllithium have been studied in order to gain insight into the factors involved in the competition between ring methylation and side-chain metalation.189 The major product from the reaction of 2,5-dimethylpyrazine and ethereal methyllithium was shown to be trimethylpyrazine, thus confirming Klein and Spoerri s earlier observation.190,191 Tetramethylpyrazine was also formed as a by-product. Proof of side-chain metalation was obtained by treatment of the reaction mixture with methyl benzoate and isolation of 2-methyl-5-phenacylpyrazine. Evidence for the presence of dihydro-and tetrahydropyrazine intermediates is derived from the infrared spectrum of the crude product obtained on hydrolysis of the reaction mixture which shows C=N and N-H absorptions (see Scheme 17). 

Reactions of the isomeric dimethylpyrazines and trimethylpyrazines with methyllithium have been studied in detail (635). Metalation of the side chain of... 

Dimethylpyrazine and ethereal methyllithium, treated with diethyl carbonate, gave 2-ethoxycarbonylmethyl-3-methylpyra2ine (635) and 2,3-dimercapto-5,6-dimethylpyrazine refluxed with methyl chloroformate in benzene gave 2,3-bis(methoxycarbonyl)thio-5,6-dimethylpyrazine (27) (1145). 

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